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Clark Lindgren
Professor of Biology
B.S., Physics, Wheaton College M.S., Ph.D., Physiology,
University of Wisconsin-Madison Postdoctorate, Neurobiology, Duke University
Tel: 641-269-3041; FAX: 641-269-4285;
Office: Science 2010; Email: lindgren@grinnell.edu
Neuroscience Web Site
In my laboratory we study the chemical synapse, a specialized junction where
neurons communicate with adjacent cells, such as sensory receptors, muscle
cells, or other neurons. We are trying to understand how the presynaptic cell at a
chemical synapse controls the release of its messenger molecule, the
neurotransmitter, and how this process can be modified by synaptic activity. Since
calcium ions have been clearly implicated in the initiation of neurotransmitter release,
one of our goals is to learn more about how presynaptic nerve terminals regulate
intracellular calcium. We have also studied how metabotropic acetylcholine receptors,
nitric oxide, and endocannabinoids modifies the release of neurotransmitter; how
synaptic vesicles, which package neurotransmitter molecules, are recycled back into
the presynaptic cell following the release of neurotransmitter; and how glial cells
(the "supporting" cells of the nervous system) are influenced by synaptic activity
and, in turn, modulate the release of neurotransmitter.
Current Working Model of the Vertebrate Neuromuscular Junction
This model represents our current understanding of
the signaling pathways involved in muscarine-induced synaptic depression at the
vertebrate NMJ along with some speculation as to the pathways that may be involved
in synaptic enhancement (the data supporting these latter speculations are not
included on this poster). Block arrows represent the diffusion or transport of a
signaling molecule. Curved block arrows indicate an enzymatic conversion. Solid
black arrows depict steps that have been experimentally verified, whereas dashed
arrows reveal steps that contain unknown details or hypothesized relationships. All
chemicals in italics and their respective arrows are meant to show the targets of the
experimental reagents used. We are not sure whether NO is produced in the muscle
fibers or the PSCs so we have included each possibility and noted both with (*).
NO, acting via PKG, is necessary but not sufficient to modulate neurotransmitter
release and we have noted this with a dashed line and (&). We do not yet know
the specific target of PKG. The presence of COX-2 in the muscle, the M1 influence
on COX-2 and the mechanism of PGE2-G action are all based on preliminary data
(not shown in this poster). Abbreviations: intracellular calcium transient (?[Ca2+]i),
acetylcholine (ACh), nicotinic acetylcholine receptor (nAChR), muscarinic
acetylcholine receptor subtype 3 (M3), G-protein (G), phosphatidylinositol or its
phosphorylated derivatives (PI), phospholipase C (PLC), diacylglycerol (DAG),
diacylglycerol lipase (DGL), 2-arachidonylglycerol (2-AG), cannabinoid receptor
subtype 1 (CB1), nitric oxide synthase (NOS), nitric oxide (NO), guanosine
triphosphate (GTP), soluble guanylate cyclase (sGC), cyclic guanosine
monophosphate (cGMP), cGMP-dependant protein kinase (PKG),
cyclooxygenase-2 (COX-2), prostaglandin E2 glycerol (PGE2-G).
Most of our experiments are carried out on the specialized synapse between a
motor nerve and muscle cell, called the neuromuscular junction. We study this
synapse in several different animals, including frogs, crayfish and lizards, with
the actual preparation used depending on the specific needs of the project. The
techniques that we use include both intracellular and extracellular recording of
electrical activity in the nerve and muscle. We also use optical methods to monitor
various cellular parameters, such as intracellular calcium activity, pH, endocytosis, etc.
- Zachary Newman, Priya Malik, Tse-Yu Wu, Christopher Ochoa, Nayantara Watsa and Clark A. Lindgren (2007). Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction. European Journal of Neuroscience 25, 1619-1630.
- Austin R. Graves, Katherine A Lewin, & Clark A. Lindgren (2004). Nitric Oxide, cAMP and the biphasic muscarinic modulation of ACh release at the lizard neuromuscular junction. The Journal of Physiology 559, 421-430.
- Clark A. Lindgren, Dennis G. Emery, and Philip G. Haydon (1997) "Intracellular Acidification Reversibly Reduces Endocytosis at the Neuromuscular Junction." The Journal of Neuroscience, 17(9) 3074-3084. [Abstract]
- Clark A. Lindgren and Melissa V. Laird (1994) "Nitroprusside Inhibits Neurotransmitter Release at the Frog Neuromuscular Junction." NeuroReport 5, 2205-2208.
- Fall
BIO-150: Introduction to Biological Inquiry - "The Language of Neurons"
- Spring
- Biology 135: Structure and Function of Organisms
- Biology 150: Introduction to Biological Inquiry "The Language of Neurons"
- Biology 236 The Biology of Cells
- Biology 251: Molecules, Cells, and Organisms
- Biology 363: Neurobiology
- Biology 364: Animal Physiology
- Neuroscience 250: Neuroscience Foundations, Future, & Fallacies
- Tutorial: "Acrimony, Authority, and Assumptions"
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